GENE-THERAPY FOR HEMOPHILIA-B - HOST IMMUNOSUPPRESSION PROLONGS THE THERAPEUTIC EFFECT OF ADENOVIRUS-MEDIATED FACTOR-IX EXPRESSION

Hemophilia B is caused by a deficiency of blood clotting factor IX (FI X), Previous studies have shown that the delivery of a recombinant ade noviral vector expressing canine FIX (cFIX) resulted in a complete cor rection of hemophilia B in FIX-deficient dogs, but that cFIX expressio n decreased to only about 1-2% of normal levels 3 weeks after treatmen t, In the present study, therapeutic levels of cFIX expression capable of producing a partial correction of hemophilia B were maintained for at least 6 months after the coadministration of the cFIX-expressing a denovirus and the immunosuppressive agent cyclosporin A (CsA), These f indings support a recent report (Yang et al., 1994) that host T-cell-m ediated immunity against virally transduced cells is a major contribut ing factor to the transient nature of adenovirus-mediated gene express ion in immunocompetent animals, Although a second administration of th e cFIX-expressing adenovirus 6 months after the first infusion had onl y a minimal effect on plasma FIX levels in a dog that had been continu ously treated with CsA, the prolonged expression of the transgene indi cates that immunosuppression may be applicable in attaining long-term treatment of clinically relevant disorders.